Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment on the basis of physicochemical properties and available toxicological data, as recommended by ECHA Guidance R7.c
Adequacy of study:
key study
Study period:
2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
absorption
distribution
excretion
metabolism
toxicokinetics
Principles of method if other than guideline:
Assessment on the basis of physicochemical properties and available toxicological data, as recommended by ECHA Guidance R7.c
GLP compliance:
no

Absorption

Oral/gastrointestinal absorption:

Oral/gastrointestinal absorption:

Based on the molecular weight of 852.16 g/mol for REACTIVE RED 218, it can be assumed to have moderate oral absorption. However with the high water solubility of 296 g/L, REACTIVE RED 218may readily dissolve into the gastrointestinal fluids and be absorbed via passive diffusion.

In two acute oral toxicity studies with REACTIVE RED 286, several mortalities and clinical signs were seen, which indicates absorption taking place from the gastrointestinal tract.

In the 28-days repeated dose toxicity study with the structurally similar substance REACTIVE RED 286,red stained feces were noted in males and females at all dose levels (100, 300 and 1000 mg/kg bw/day). Red discoloration was also detected macroscopically in multiple organs, like kidneys, mesenteric lymphnodes and stomach.

In the micronucleus assay withstructurally similar substance REACTIVE RED 286, the animals showed discoloured urine after treatment with 2000 mg/kg b.w. indicating the bioavailability of the substance.

These findings were again indicative of absorption taking place from the gastrointestinal tract.Hence, on the basis of hydrophilic nature and the findings of the toxicological studies as discussed above, REACTIVE RED 218 is expected to be absorbed by the gastrointestinal tract when administered orally.

Dermal absorption:

Based on the molecular weight of 852.16g/mol for REACTIVE RED 218, poor dermal absorption is expected. With high solubility in water (296 g/L) and low partition coefficient (-3.06), dermal uptake is expected to be low as REACTIVE RED 218can be considered to be too hydrophilic to cross the lipid rich environment of thestratum corneum. The surface tension of 66.3 mN/m for REACTIVE RED 218 also suggests a low dermal uptake from skin surfaces.

REACTIVE RED 218 is neither corrosive nor irritating to the skin as well as eyes, while, it was not sensitising to the skin. Hence, the experimental data also suggests a low dermal uptake.However, the findings from the acute oral toxicity with REACTIVE RED 218 and repeated dose oral toxicity study with REACTIVE RED 286, indicates the potential for absorption following ingestion and it is therefore possible that the substance will also be absorbed if it is exposed dermally. Nonetheless, absorption will be limited and only substantial at higher dosage and the test substance will be quickly excreted owing to the high water solubility.

Respiratory absorption:

REACTIVE RED 218 is expected to have low volatility based on the low vapour pressure (<2.4 x 10-5Pa at 25 °C), and hence may not be available for inhalation as a vapour. Further, the high water solubility (296 g/L), indicates if vapours are produced will be trapped in the mucus. However, the effects observed in the acute oral toxicity study with REACTIVE RED 218 as well as repeated dose oral toxicity study with the structurally similar substance REACTIVE RED 286, along with the median aerodynamic diameter of24.68 µm, indicate the potential for absorption following ingestion and it is therefore possible that the substance will also be absorbed if it is inhaled. Nonetheless, absorption will be limited and only substantial at higher dosage and the test substance will be quickly excreted owing to the high water solubility.

Distribution

Systemic distribution due to the high water solubility would most likely occur via the serum. Owing to the high molecular size and hydrophilic nature of the substance (low n-octanol/water partition coefficient and high water solubility), access of REACTIVE RED 218to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers, whileaccumulation in body fat is unlikely to occur.

Metabolism

In the genetic toxicity studies including bacterial reverse mutation assays with REACTIVE RED 218, mammalian cell gene mutation assay with REACTIVE RED 286 and available toxicity studies, there was no evidence to indicate REACTIVE RED 218 or metabolite influenced hepatic metabolism. However, in a chromosomal aberration test with Chinese hamster lung fibroblasts (V79), the structurally similar substance REACTIVE RED 286, was found to be clastogenic in the absence of metabolic activation, while it was not clastogenic in the presence of metabolic activation. This indicates hepatic metabolism may lead to reduced toxicity, however, it should be taken into consideration that rat S9 fraction is not equivalent to the human metabolism.

Further the high water solubility of REACTIVE RED 218 suggests that metabolism would be limited and not required to facilitate renal excretion.

Excretion

Route of excretion for REACTIVE RED 218 has not been investigated. However owing to the hydrophilic nature of the substance, it will be expected to be predominantly excreted via urine, while any unabsorbed remaining fraction being excreted in the feces.

Conclusions:
REACTIVE RED 218 would be absorbed primarily in gastrointestinal tract, while limited absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and not required to facilitate renal excretion.
Executive summary:

REACTIVE RED 218 would be absorbed primarily in gastrointestinal tract, while limited absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and not required to facilitate renal excretion.

Description of key information

REACTIVE RED 218 would be absorbed primarily in gastrointestinal tract, while limited absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and not required to facilitate renal excretion.

Key value for chemical safety assessment

Additional information